Abstract 1557: Intratumoral plasmid IL-12 enhanced the systemic anti-tumor effect of anti-PD-1 antibody in triple-negative breast cancer

Abstract

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive disease with limited therapeutic options. Although immune checkpoint inhibitors (ICI) have entered the therapeutic landscape in TNBC, their benefits are limited to a minority of patients. We hypothesized the combination of ICI with the intratumoral administration of plasmid IL-12 (tavokinogene telseplasmid; TAVOTM) followed by electroporation could enhance the therapeutic efficacy based on our previous observation of the anti-tumor effect of TAVO in TNBC. The purpose of this study was to clarify the potency of TAVO as an additive local treatment to systemic anti-PD-1 immunotherapy. Methods: A murine TNBC cell line, E0771, was implanted bilaterally into flanks of female C57BL/6 mice, which were randomized into four groups: control (control plasmid + control antibody), anti-PD-1 (control plasmid + anti-PD-1), Tavo (Tavo + control antibody), and combination (TAVO + anti-PD-1). TAVO or control plasmid (50 µg/injection) was administered into a single tumor followed by electroporation on days 0, 3, and 7, as we previously reported (SITC abstract), while tumors on the other side were left untreated. Anti-PD-1 or control antibody (200 µg/injection) was administered by intraperitoneal injection on days 2, 6, 9, and 13. Tumor volume was measured every other day, and the survival of mice was monitored. The local microenvironment of both treated and untreated tumors and systemic effect on splenocytes were evaluated using flow cytometry and single-cell RNA-sequencing. Results: The combination of intratumoral administration of TAVO with anti-PD-1 suppressed the tumor growth more effectively compared to the other groups not only in treated local tumors but also in untreated remote tumors. Higher rates of tumor regression and better survival were observed in the combination group. TAVO locally increased effector CD8+ T cells while reducing regulatory T cells in both treated tumors and distant untreated tumors. The systemic expansion of effector CD8+ T cells was also observed in splenocytes. Conclusions: Intratumoral electroporation of TAVO with anti-PD-1 improved systemic anti-tumor efficacy by modifying the immunosuppressive tumor microenvironment. Clinical studies of this combination treatment in TNBC are underway. Citation Format: Hiroshi Nagata, Takuya Osada, Erika J. Crosby, David A. Canton, Chris G. Twitty, H. Kim Lyerly. Intratumoral plasmid IL-12 enhanced the systemic anti-tumor effect of anti-PD-1 antibody in triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1557.